Establishing An Integrated Molecular Signature Model For Metastatic Prostate Cancer

UroToday.com - Genomic and proteomic profiling has attempted to link patients with the likelihood for advanced disease progression. Approaches to do this are reviewed by Dr. Taylor and associates in the June 1, 2006 issue of Cancer Research.

Integrated approaches are of three types. One uses data available in the public domain rather than experimental, patient derived data and uses data-mining and bioinformatics. A second model integrates experimental data with heterogeneous public data sources. The third approach integrates multifaceted genomic and proteomic data for analysis of metastatic risk.

The paper reviews the integrated approach from the laboratory of Dr. Arul Chinnaiyan at the University of Michigan. Specimens from patients include benign, localized malignant and metastatic tissues that undergo direct proteomic analysis by an antibody-based high-throughput immunoblot approach. This methodology was validated with traditional immunoblotting and tissue microarray-based immunohistochemical staining. Correlation was also performed with prostate cancer transcriptomes to include publicly available genes expression studies and microarrays. Mapping between genes and dysregulated proteins resulted in data for meta-analysis by statistical procedures.

A 50-gene ensemble was identified that served as a multiplex signature of CaP progression when it was applied to patient primary disease specimens. The 50-gene signature was tested with two CaP gene expression studies and demonstrated strong concordance. The data suggests that mRNA transcripts that correlate with protein levels in metastatic disease could be applied as a multiplex gene predictor of CaP progression in localized disease. Application to other primary tumor types also supported relevance.

The integration of high-throughput data could also be extended to other proteomic platforms, such as mass spectrometry or array-based platforms.

By Christopher P. Evans, MD

Reference:
Cancer Res 2006;66:5537-39
Link Here.
Taylor BS, Varambally S, Chinnaiyan AM

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